title: Nasal PMN response to repeated challenge with endotoxin in healthy volunteers.
abstract: BACKGROUND
  We have employed nasal challenge with lipopolysaccharide (LPS) followed by nasal lavage (NL) to experimentally induce and examine upper airway inflammation in human volunteers. It is unclear however whether adaptation within individuals occurs following repeated nasal challenge. This was a pilot study to determine if repeated nasal LPS challenge yields attenuation of markers of inflammation (primarily neutrophil response) in the NL fluid of healthy humans.
  
  
  METHODS
  We employed a 3-day nasal LPS challenge protocol with NL using a "split nose" design. The control and LPS nares received two consecutive day saline (0.9% saline/day) and LPS (2 µg LPS/day) challenges, respectively followed by an LPS (2 µg/day) challenge to each nare on Day 3. NL was performed immediately pre Day 1 challenges and 6-h post nasal LPS challenges on both Days 1 and 3. Markers of inflammation (PMNs/mg, cytokines) were assessed in NL and the inflammatory response to LPS (measured as the difference between pre and post challenge) was evaluated in both nares on Day 3 and compared to Day 1.
  
  
  RESULTS
  Significant (p < 0.05) blunting of the LPS-induced polymorphonuclear leukocyte (PMN) response was observed in the nare that received repeated LPS challenges as compared to the control nare (67.60  ±  22.39 vs. 157.8  ±  76.04 PMN/mg) and initial LPS challenge on Day 1 (121 ± 32 PMN/mg). Decreased soluble CD14 and significantly decreased interleukin-8 were also found in the repeat LPS-treated nare. In the LPS-treated nare, the blunted PMN response on Day 3 correlated well with the observed PMN response on Day 1 (r = 0.58, p = 0.02).
  
  
  CONCLUSIONS
  We show attenuation of PMN response to repeated LPS in the nasal airways in healthy humans. Effect of repeat endotoxin exposure prior to allergen delivery on local airway inflammation in both healthy and atopic subjects can be studied.
authors.affiliation: Department of Pediatrics, Clinical Fellow, Allergy Immunology, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Vinod
authors.initials: V
authors.lastname: Doreswamy
authors.forename: Neil E
authors.initials: NE
authors.lastname: Alexis
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhou
authors.forename: David B
authors.initials: DB
authors.lastname: Peden
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D002452:Cell Count; D016207:Cytokines / Q000032:analysis; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D016209:Interleukin-8 / Q000032:analysis; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008297:Male; D008875:Middle Aged; D017817:Nasal Lavage Fluid / Q000737:chemistry / Q000166:cytology*; D009299:Nasal Provocation Tests; D009504:Neutrophils / Q000276:immunology*; D052638:Particulate Matter / Q000633:toxicity*; D010865:Pilot Projects; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000517:prevention & control; D055815:Young Adult
chemical_list: D015415:Biomarkers; C508606:CXCL8 protein, human; D016207:Cytokines; D004731:Endotoxins; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D052638:Particulate Matter